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Thursday, January 13, 2011

Just like underwater cables, DNA moves about in an aqueous environment, buffeted by currents and thermal energy. Understanding the stress mechanics of DNA could lead to clues about gene expression. Credit: istockphoto.com/rustycloud.

By Carol Clark

DNA is like an underwater cable. This pivotal idea occurred to mechanical engineer Sachin Goyal while he was a researcher at the University of Michigan. Working in the lab of Noel Perkins, Goyal was investigating the dynamics of steel cables mounted with acoustic sensors that are used by the U.S. military to monitor enemy submarines. The cables are attached to the seabed on one end, and to surface buoys on the other.

“Currents cause the buoys to rotate, twisting the cables,” explains Goyal, who is now a post-doctoral fellow in the Emory physics department. “The cables can get entangled and form loops that weaken them.”

The Navy needed to predict how the cables would bend and deform, or “hockle,” under different conditions. It’s the same principle as the compression load of a steel beam in a building, but instead of analyzing force applied to a straight rod, you have to factor in loops and twists.

Graphic: Noel Perkins, University of Michigan.

“It’s a mathematically challenging problem,” Goyal says. He developed a nonlinear theory for dynamic deformations of a rod, and the first computational model to simulate the mechanics of filament-like structures, to help engineers design optimal layouts for the undersea cables.

“I started thinking, ‘The kind of deformations that happen to underwater cables are the same that occur in DNA molecules,” Goyal recalls.

The revelation opened a whole new area of research for Goyal. Last year he joined the lab of Emory physicist Laura Finzi, who investigates the thermodynamics and kinetics of structural changes in DNA. Understanding these changes in DNA, the blueprints for all living organisms, is crucial to coming up with drug and vaccine design, and new technologies for genetic engineering and disease control.

After simulating the dynamics of the deformation of an undersea cable, Goyal showed that the same principle applied equally well to DNA looping. The simulation captures the complete dynamics, not just a static behavior.

Just like underwater cables, DNA moves about in an aqueous environment, buffeted by currents and thermal energy. But while buckling and twisting are bad for underwater cables, they are much desired for DNA.

The entire human chromosome is a meter long, but it must pack inside a cell nucleus that is a few microns in diameter. The double-helical filament wraps over itself to form a superhelix so that it can fit into this microscopic space.

“DNA is always fluctuating, forming loops and straightening, which causes the DNA filament to become more or less accessible, turning genes on and off,” Goyal says. “My hypothesis is that you can predict where loops will form and where the DNA will be accessible if you understand the stress mechanics of DNA. Stress distribution may play a crucial role in gene expression.”Sachin Goyal uses magnetic tweezers to tease out mechanical properties of DNA. Photo by Carol Clark.

The Journal of Physics recently published an Emory study focused on how one protein, known as C1, alters the mechanical behavior of DNA. “This protein can cling anywhere along DNA and as it clings, it causes the DNA to contract,” Goyal says. “The more proteins that bind to the DNA, the more contracted the DNA becomes.”

Previous research has shown that the C1 protein plays a role in sparking transitions between dormant and infectious states of viruses within a bacterial host. “We measured the contraction of the DNA, while measuring how much C1 was clinging to it,” Goyal explains. “One idea is that, by using such measurements, we could develop a model with which to explore when a pathogen might switch from a dormant to infectious stage.”